Exploring the plasticity of the InhA substrate-binding site using new diaryl ether inhibitors.
Diaryl ethers
InhA
Inhibitors
Minor portal
Tuberculosis
X-ray crystallography
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
12 Dec 2023
12 Dec 2023
Historique:
received:
09
11
2023
revised:
08
12
2023
accepted:
10
12
2023
medline:
22
12
2023
pubmed:
22
12
2023
entrez:
21
12
2023
Statut:
aheadofprint
Résumé
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a worldwide scourge with more than 10 million people affected yearly. Among the proteins essential for the survival of Mtb, InhA has been and is still clinically validated as a therapeutic target. A new family of direct diaryl ether inhibitors, not requiring prior activation by the catalase peroxidase enzyme KatG, has been designed with the ambition of fully occupying the InhA substrate-binding site. Thus, eleven compounds, featuring three pharmacophores within the same molecule, were synthesized. One of them, 5-(((4-(2-hydroxyphenoxy)benzyl)(octyl)amino)methyl)-2-phenoxyphenol (compound 21), showed good inhibitory activity against InhA with IC
Identifiants
pubmed: 38128204
pii: S0045-2068(23)00693-4
doi: 10.1016/j.bioorg.2023.107032
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
107032Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.